PNPO Deficiency and Cirrhosis: Expanding the Clinical Phenotype?

Abstract

We report the case of a 4-year-old boy with pyridoxamine 5-phosphate oxidase deficiency, now the second reported case to develop hepatic cirrhosis. He presented with an encephalopathy in the first 1.5 h of life and received a first dose of PLP at 40 h of life. PNPO gene sequencing identified homozygosity for a novel variant in exon 7, c.637C>T (p.Pro213Ser). Persistent elevations in alanine transferase and aspartate transferase combined with an echogenic liver on ultrasound prompted performance of a liver biopsy which demonstrated hepatic cirrhosis. This is the second reported case of hepatic cirrhosis in PNPO deficiency. The pathogenesis is unclear but may be related to epigenetic activation of purinergic signaling in the hepatic stellate cells. PNPO deficiency may in time prove to be a suitable candidate for consideration of therapeutic orthotropic liver transplantation in select patients.JIMD Rep. 2013;9:139-42. (PMID: 23430561); Am J Physiol Gastrointest Liver Physiol. 2004 Aug;287(2):G417-24. (PMID: 14764443); J Inherit Metab Dis. 2007 Feb;30(1):96-9. (PMID: 17216302); Dev Med Child Neurol. 2010 Jul;52(7):e133-42. (PMID: 20370816); FASEB J. 1991 Mar 1;5(3):271-7. (PMID: 2001786); Brain. 2014 May;137(Pt 5):1350-60. (PMID: 24645144); JIMD Rep. 2014;17:67-70. (PMID: 25256445); In Vivo. 2007 Nov-Dec;21(6):957-65. (PMID: 18210741); Cell Signal. 2013 Sep;25(9):1837-44. (PMID: 23707524); J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):317-26. (PMID: 16763894); Mol Genet Metab. 2014 Apr;111(4):418-27. (PMID: 24495602); Hepatobiliary Pancreat Dis Int. 2012 Oct;11(5):545-8. (PMID: 23060403); Epilepsy Behav. 2011 Mar;20(3):494-501. (PMID: 21292558); Neuropediatrics. 2014 Feb;45(1):64-8. (PMID: 24297574); Hepatology. 2014 Oct;60(4):1418-25. (PMID: 24633972); Hum Mol Genet. 2005 Apr 15;14(8):1077-86. (PMID: 15772097); Drug Dev Res. 2001 Aug;53(4):281-291. (PMID: 27134334); J Biol Chem. 2000 Jan 28;275(4):2247-50. (PMID: 10644669); Mol Genet Metab. 2008 Aug;94(4):431-4. (PMID: 18485777); Mol Genet Metab. 2008 Feb;93(2):216-8. (PMID: 18024216); Neurology. 2014 Apr 22;82(16):1425-33. (PMID: 24658933); Dev Med Child Neurol. 2014 May;56(5):498-502. (PMID: 24266778); Arch Dis Child Fetal Neonatal Ed. 2008 Mar;93(2):F151-2. (PMID: 18296573); J Pharmacol Exp Ther. 2015 Jan;352(1):2-13. (PMID: 25362107); Hepatology. 2011 Jan;53(1):193-201. (PMID: 21254170). Linking ISSN: 21928304. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2015 Jun 25. Current Imprints: Publication: 2019- : [Hoboken, NJ] : Wiley; Original Imprints: Publication: Berlin : SSIEM and Springer-Verlag, c2011. <br />